Effects of a new cholinolytic drug of tropanes and its optical isomers on central muscarinic and nicotinic receptors

Pharmacol Res. 1995 Sep;32(3):105-9. doi: 10.1016/s1043-6618(05)80001-5.

Abstract

2 alpha-(2',2'-disubstituted-2'-hydroxy-ethoxy)tropane (2 alpha-DHET cholinolytic, is a racemic tertiary amine with two chiral carbonic atoms. It has four optical isomers whose absolute configurations are 1R-2 alpha-2'S, 1R-2 alpha-2'R 1S-2 alpha'R and 1S-2 alpha-2'S. These compounds showed both antimuscarinic and antinicotinic activity, blocking both muscarinic and nicotinic receptors. Central muscarinic receptors, rather than nicotinic receptors, have a stereoselective specificity to these compounds. The 2'R configurations are more suitable to the stereostructure of the binding site of muscarinic receptors than the 2'S configuration.

MeSH terms

  • Animals
  • Body Weight
  • Female
  • Male
  • Molecular Conformation
  • Muscarinic Antagonists / metabolism
  • Prosencephalon / chemistry
  • Prosencephalon / metabolism*
  • Quinuclidinyl Benzilate / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / metabolism*
  • Receptors, Nicotinic / metabolism*
  • Tropanes / chemistry
  • Tropanes / metabolism*

Substances

  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • Tropanes
  • 2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyethoxy)tropane
  • Quinuclidinyl Benzilate